Format

Send to

Choose Destination
PLoS One. 2013 Oct 9;8(10):e77020. doi: 10.1371/journal.pone.0077020. eCollection 2013.

Solution NMR structure and histone binding of the PHD domain of human MLL5.

Author information

1
Northeast Structural Genomics Consortium and Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.

Abstract

Mixed Lineage Leukemia 5 (MLL5) is a histone methyltransferase that plays a key role in hematopoiesis, spermatogenesis and cell cycle progression. In addition to its catalytic domain, MLL5 contains a PHD finger domain, a protein module that is often involved in binding to the N-terminus of histone H3. Here we report the NMR solution structure of the MLL5 PHD domain showing a variant of the canonical PHD fold that combines conserved H3 binding features from several classes of other PHD domains (including an aromatic cage) along with a novel C-terminal α-helix, not previously seen. We further demonstrate that the PHD domain binds with similar affinity to histone H3 tail peptides di- and tri-methylated at lysine 4 (H3K4me2 and H3K4me3), the former being the putative product of the MLL5 catalytic reaction. This work establishes the PHD domain of MLL5 as a bone fide 'reader' domain of H3K4 methyl marks suggesting that it may guide the spreading or further methylation of this site on chromatin.

PMID:
24130829
PMCID:
PMC3793974
DOI:
10.1371/journal.pone.0077020
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center